P1240: MICROBIOME DIVERSITY IN PATIENTS WITH LYMPHOMA
Authors: Lucie Dlouha, Marketa Tenglerova, Johana Rehakova, Michaela Brichova, Martin Kostovcik, Katerina Benesova, Miloslav Kverka, Jarmila Heissigerova, Petra Svozilkova, Iva Ondeckova, Jana Senavova, Vaclav Herman, Klara Kostovcikova, Marek Trneny
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: The Non-Hodgkin’s lymphomas (NHL) evolution, progression and the response to the therapy could be connected with immune evasion mechanism. Microbiota composition is associated with the host immune regulation. It is studied in different diseases, in the context of different types of immunotherapy and immune reactivity. The data on oral microbiota (oralM) as well as gastrointestinal microbiota (gutM) in NHL are still limited (Diefenbach et al., 2021 and Yuan et al., 2021). We have decided to run a prospective study comparing the microbiota composition in patients (pts) with different lymphoma subtypes and its impact on treatment in pts with different lymphoma subtypes. Aims: The aim of this study part was to study oralM and gutM diversity in the group of pts with lymphoma – mainly Diffuse Large B-Cell Lymphoma (DLBCL) and Primary Central Nervous System Lymphoma/Vitreoretinal Lymphoma (PCNSL/VRL), and to compare it with controls (CON). Methods: The inclusion criteria were newly diagnosed lymphoma, including DLBCL, PCNSL/VRL and other NHL. The diagnostic and clinical data were collected. The fresh fecal samples and buccal swab samples were collected from pts as well as from healthy CON Bacterial 16S ribosomal RNA gene sequencing by Illumina approach was used to identify the different species that comprise the gutM and oralM. Sequencing data were processed using QIIME tool. For α-diversity analysis, Shannon Diversity index was used to compare pts with lymphoma vs. CON. Principle Coordinate Analysis (PCoA) based on weighted UniFrac distance was used to describe β-diversity. The permutational multivariate analysis of variance (PERMANOVA) pseudo-F test was used for determination of statistical differences among groups. Linear discriminant analysis Effect Size (LEfSe) was used to analyze differences in microbial abundances between groups. Results: Altogether 59 pts with lymphoma (32 DLBCL pts, 23 PCNSL/VRL pts, 4 other NHL, median age was 67 years (same as for pts with DLBCL either PCNSL), males 35 (59%)) and 10 CON (median age 67 years, 2 (20%) males) were enrolled in the period Dec 2019 until Jan 2022. Out of DLBCL pts non-GC subtype was found in 20 pts (63%) and risk IPI 3-5 in 27 pts (84%). Out of 17 PCNSL DLBCL pts with histological diagnosis non-GC phenotype was found in 7 pts (41%), GC in 5 (29%) and in 5 (29%) pts the results were not conclusive. Out of 18 evaluable PCNSL 15 (83%) pts had intermediate or high risk according to MSKCC score. Lymphoma pts have a significantly higher α-diversity of their oralM than CON (p<0.002) and also exhibit a significant shift in β-diversity (p<0.027). This shift is mainly caused by an increased relative abundance of pathobionts, such as the order Fusobacteriales and Prevotella spp., in lymphoma pts. On the other hand, although lymphoma pts have significantly decresed α-diversity of the gutM (p<0.019), they do not differ in β-diversity from CON. Nevertheless, they have significantly higher abundance of microbes related to the Escherichia/Shigella and Ruminococcus gnavus groups. Summary/Conclusion: This finding of the study represents the important piece of evidence for understanding the microbiota diversity between lymphoma pts and CON. It will serve as basis for further correlative analysis with treatment outcome. Interestingly there was shift for higher diversity in oralM and lower diversity in gutM. The study is supported by the Cooperation Program, research area“Oncology and Haematology” and NU20-03-00253 and NU22-03-00370.Keywords: Lymphoma, B cell lymphoma